Comparison of a one-time educational intervention to a teach-to-goal educational intervention for self-management of heart failure: design of a randomized controlled trial.
Heart failure (HF) is common, costly and associated with significant morbidity and poor quality of life, particularly for patients with low socioeconomic status. Self-management training has been shown to reduce HF related morbidity and hospitalization rates, but there is uncertainty about how best to deliver such training and what patients benefit. This study compares a single session self-management HF training program against a multiple session training intervention and examines whether their effects differ by literacy level. In this randomized controlled multi-site trial, English and Spanish-speaking patients are recruited from university-affiliated General Internal Medicine and Cardiology clinics at 4 sites across the United States. Eligible patients have HF with New York Heart Association class II-IV symptoms and are prescribed a loop diuretic. Baseline data, including literacy level, are collected at enrollment and follow-up surveys are conducted at 1, 6 and 12 months. Upon enrollment, both the control and intervention groups receive the same 40 minute, literacy-sensitive, in-person, HF education session covering the 4 key self-management components of daily self assessment and having a plan, salt avoidance, exercise, and medication adherence. All participants also receive a literacy-sensitive workbook and a digital bathroom scale. After the baseline education was completed, patients are randomly allocated to return to usual care or to receive ongoing education and training. The intervention group receives an additional 20 minutes of education on weight and symptom-based diuretic self-adjustment, as well as periodic follow-up phone calls from the educator over the course of 1 year. These phone calls are designed to reinforce the education, assess participant knowledge of the education and address barriers to success.The primary outcome is the combined incidence of all cause hospitalization and death. Secondary outcomes include HF-related quality of life, HF-related hospitalizations, knowledge regarding HF, self-care behavior, and self-efficacy. The effects of each intervention will be stratified by patient literacy, in order to identify any differential effects. Enrollment of the proposed 660 subjects will continue through the end of 2009. Outcome assessments are projected to be completed by early 2011. ClinicalTrials.gov (http://www.clinicaltrials.gov/) NCT00378950.


Erythropoietin immunolocalization in renal cell carcinoma.
Erythropoietin (EPO) is a well-recognized hormone that induces erythrocytosis in a wide range of physiologic and pathologic situations in mammals. One of these situations is a paraneoplastic erythrocytosis, which might be seen in association with various neoplasms, including renal cell carcinoma (RCC), hepatoma, and cerebellar hemangioblastoma. Although there have been multiple studies confirming the association between this erythrocytosis and the production of EPO by tumor cells, immunohistochemical detection of EPO in formalin-fixed, paraffin-embedded tissue was not described. We report on the use of microwave antigen retrieval to detect EPO in RCCs in such routinely processed tissues. We selected 19 RCCs received as nephrectomy specimens, fixed in formalin, and routinely processed. These cases were previously diagnosed on the basis of morphologic, immunohistochemical, and clinical features. We examined the immunoreactivity of these specimens with a monoclonal anti-EPO antibody. Fetal (20 wk gestational age) liver served as a positive control. Intense positive immunoreactivity was observed as cytoplasmic, granular staining in fetal hepatocytes. Fourteen RCCs (10 clear cell and 4 tubulopapillary types) demonstrated unequivocal cytoplasmic immunoreactivity. Additionally, two clear cell tumors were only focally positive, whereas three (16%) were negative. EPO immunoreactivity might thus prove to be of value in the diagnosis or confirmation of RCC, particularly in the context of routinely processed material.


Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles.
The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization. Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization. Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinization, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone. The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize.


Testing multi-alternative decision models with non-stationary evidence.
Recent research has investigated the process of integrating perceptual evidence toward a decision, converging on a number of sequential sampling choice models, such as variants of race and diffusion models and the non-linear leaky competing accumulator (LCA) model. Here we study extensions of these models to multi-alternative choice, considering how well they can account for data from a psychophysical experiment in which the evidence supporting each of the alternatives changes dynamically during the trial, in a way that creates temporal correlations. We find that participants exhibit a tendency to choose an alternative whose evidence profile is temporally anti-correlated with (or dissimilar from) that of other alternatives. This advantage of the anti-correlated alternative is well accounted for in the LCA, and provides constraints that challenge several other models of multi-alternative choice.


High efficiency nano-focusing kinoform optics for synchrotron radiation.
Modern synchrotron sources have provided for decades intense beams of photons over a large energy spectrum. The availability of improved optics and detectors has opened up new opportunities for the study of matter at the micrometre and nanometre scale in many disciplines. Whilst exploitation of micro-focused beams occurs almost daily in many beamlines, the production of beams of 100 nm is achieved on few instruments which use specialised optics. Refractive lenses, zone plates, curved mirrors, multilayers, and multilayer Laue lenses, can all focus x-rays to less than 50 nm under strict beam stability conditions. Focusing the synchrotron radiation to beam sizes smaller than 10 nm is considered the ultimate goal for the current decade. Silicon micro-technology has so far provided some of the most advanced x-ray refractive lenses; we report on design and characterisation of a novel silicon kinoform lens that is capable of delivering nano-beams with high efficiency.


Influence of a dopamine pathway additive genetic efficacy score on smoking cessation: results from two randomized clinical trials of bupropion.
To evaluate the associations of treatment and an additive genetic efficacy score (AGES) based on dopamine functional polymorphisms with time to first smoking lapse and point prevalence abstinence at end of treatment among participants enrolled into two randomized clinical trials of smoking cessation therapies. Double-blind pharmacogenetic efficacy trials randomizing participants to active or placebo bupropion. Study 1 also randomized participants to cognitive-behavioral smoking cessation treatment (CBT) or this treatment with CBT for depression. Study 2 provided standardized behavioural support. Two hospital-affiliated clinics (study 1), and two university-affiliated clinics (study 2). A total of 792 self-identified white treatment-seeking smokers aged ≥18 years smoking ≥10 cigarettes per day over the last year. Age, gender, Fagerström Test for Nicotine Dependence, dopamine pathway genotypes (rs1800497 [ANKK1 E713K], rs4680 [COMT V158M], DRD4 exon 3 variable number of tandem repeats polymorphism [DRD4 VNTR], SLC6A3,3' VNTR) analyzed both separately and as part of an AGES, time to first lapse and point prevalence abstinence at end of treatment. Significant associations of the AGES (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.06-1.14, P = 0.009) and of the DRD4 VNTR (HR = 1.29, 95% CI = 1.17-1.41, P = 0.0073) were observed with time to first lapse. A significant AGES by pharmacotherapy interaction was observed (β standard error = -0.18 [0.07], P = 0.016), such that AGES predicted risk for time to first lapse only for individuals randomized to placebo. A score based on functional polymorphisms relating to dopamine pathways appears to predict lapse to smoking following a quit attempt, and the association is mitigated in smokers using bupropion.


Monitoring equity in immunization coverage.
This paper analyses trends in coverage of three doses of diphtheria-pertussis-tetanus vaccine (DPT3) by wealth groups in selected countries. It discusses the depth of disparities in coverage by wealth and changes during the 1990s. Complete assessment of equity in income and its trends have been discussed in other papers, however issues related to children's well-being have often been brushed aside because the comparable data needed to fully understand and rectify inequalities is lacking. A focal point of this paper pertains to gathering any and all information recorded about the immunization of children and then transcribing these data so that it is applicable to all countries. We analyse the technical difficulties and methodological solutions that would enable comparisons to be made between various measures of inequity taken from different surveys at two or three points in time among a variety of subpopulations in order to obtain disaggregated data. This paper argues for a simultaneous analysis of changes in averages and disparities in immunization coverage along variables of interest, such as wealth, gender and place of residence in order to achieve a better understanding of trends. We also focus on measurement issues and describe trends in immunization by wealth. We conclude with a brief discussion of issues related to monitoring equitable outcomes and offer suggestions for further research. In addition, the paper presents some lessons that can be drawn about monitoring and policies. We hope that this analysis of patterns of disparities will help policy-makers in devising, proposing and executing efficient policies and interventions.


Neurophysiological basis of sympathetic nerve-preserving surgery for lower rectal cancer--a canine model.
The relative contribution and interrelated compensation of sympathetic signals among sympathetic components in pelvic plexus remain undefined. This study was designed to investigate the genitourinary function in response to autonomic nerve preservation and severance using a canine model. Eighteen mongrel dogs were randomly divided into 3 groups which received severance of the hypogastric nerves on either the right side, left side, or on both sides. The hypogastric nerves and sacral sympathetic trunks were electrically stimulated and the contraction pressure of the internal urethral orifice was measured immediately, at 1- and 3-month intervals. The ejaculation function and the length of time required to reach sexual orgasm were evaluated by manual penis-stimulation. The difference between the left and right sides of the normal hypogastric nerve in contribution to sympathetic signals was insignificant. Compared with the hypogastric nerve, the bilateral sacral sympathetic trunks were functionally trivial in controlling the closure of the internal urethral orifice. The preserved side of the hypogastric nerve compensated for the loss of sympathetic signals of the severed side within 1 month and, thereafter, remained stationary. In contrast, the functional compensation of bilateral sacral sympathetic trunks for the severed bilateral hypogastric nerves was insignificant. When the hypogastric nerve was preserved in one or both sides, all dogs maintained normal antegrade ejaculation. If bilateral hypogastric nerves were severed, 50.0% (3/6) of the dogs lost both emission and ejaculation function; 33.3% (2/6) presented with retrograde ejaculation; and, 16.7% (1/6) presented with combined retrograde ejaculation and reduced antegrade ejaculation. The time required to reach sexual orgasm was not affected by the severance of the hypogastric nerve. The normal genitourinary function could be maintained only when at least one side of the hypogastric nerve was preserved.


The effects of land use on fluvial sediment chemistry for the conterminous U.S. - results from the first cycle of the NAWQA Program: trace and major elements, phosphorus, carbon, and sulfur.
In 1991, the U.S. Geological Survey (USGS) began the first cycle of its National Water Quality Assessment (NAWQA) Program. The Program encompassed 51 river basins that collectively accounted for more than 70% of the total water use (excluding power generation), and 50% of the drinking water supply in the U.S. The basins represented a variety of hydrologic settings, rock types (geology), land-use categories, and population densities. One aspect of the first cycle included bed sediment sampling; sites were chosen to represent baseline and important land-use categories (e.g., agriculture, urban) in each basin. In total, over 1200 bed sediment samples were collected. All samples were size-limited (<63 microm) to facilitate spatial and/or temporal comparisons, and subsequently analyzed for a variety of chemical constituents including major (e.g., Fe, Al,) and trace elements (e.g., Cu, Zn, Cd), nutrients (e.g., P), and carbon. The analyses yielded total (>or=95% of the concentrations present), rather than total-recoverable chemical data. Land-use percentages, upstream underlying geology, and population density were determined for each site and evaluated to asses their relative influence on sediment chemistry. Baseline concentrations for the entire U.S. also were generated from a subset of all the samples, and are based on material collected from low population (<or=27 p km(-2)) density, low percent urban (<or=5%), agricultural or undeveloped areas. The NAWQA baseline values are similar to those found in other national and global datasets. Further, it appears that upstream/underlying rock type has only a limited effect (mostly major elements) on sediment chemistry. The only land-use category that appears to substantially affect sediment chemistry is percent urban, and this result is mirrored by population density; in fact, the latter appears more consistent than the former.


The cost of improving care: a multisite economic analysis of hospital resource use for implementing recommended postpartum contraception programmes.
The costs of quality improvement efforts in real-world settings are often unquantified. Better understanding could guide appropriate resource utilisation and drive efficiency. Immediate postpartum contraceptive care (ie, placement of an intrauterine device or contraceptive implant during hospitalisation for childbirth) represents an excellent case study for examining costs, because recommended services are largely unavailable and adoption requires significant effort. We therefore evaluated the cost of implementing immediate postpartum contraceptive services at four academic centres and one private hospital in USA. In this mixed-methods cost analysis, implementation activities were retrospectively identified using standardised data collection. Activities were categorised as preimplementation activities (infrastructure building, tool creation and stakeholder engagement) or execution activities (workforce training and process refinement). Costs were assigned based on national median salaries for the roles of individuals involved. Cross-case comparison and rapid qualitative analysis guided by the Consolidated Framework for Implementation Research were used to identify factors driving cost variation observed across sites. On average, implementation activities required 204 hours (range 119-368), with this time costing $14 433.94 (range $9955.61-$23 690.49), and involving 9 (range 7-11) key team members per site. Preimplementation activities required more resources than execution activities (preimplementation: average 173 hours, $11 573.25; execution: average 31 hours, $2860.67). Sites that used lower-cost employees (eg, shifting tasks from a physician to a project manager) observed lower costs per hour for implementation activities. Implementation activities and costs were associated with local contextual factors, including stakeholder acceptance, integration of employees and infrastructure readiness for the change effort. Our findings provide the first estimates of health system costs for adopting recommended contraceptive care in maternity units in USA. More broadly, our findings suggest that the budget impact of improvement efforts may vary widely depending on local context.


Diagnosis and management of infectious pleural effusion.
Pleural infection remains a common illness, with a high morbidity and mortality. The development of frank empyema from a simple exudative pleural effusion is a result of biochemical changes within the pleural space in response to bacterial invasion. These changes can be used in the diagnosis of pleural infection and used to predict which patients will require intercostal drainage for resolution of infection. Recent large trials in empyema have further advanced our knowledge of microbiologic patterns, informing important decisions about empiric antibacterial therapy. Diagnosis of pleural infection relies on high clinical suspicion in association with clinical features, radiology, and pleural fluid characteristics. Treatment of pleural infection is based upon accurate and often empiric choice of antibacterial agents, intercostal drainage in certain contexts, and appropriate surgical referral. Intrapleural thrombolytic therapy is not currently recommended for the treatment of pleural infection, on the basis of evidence from the largest randomized trial in empyema to date.


Short-term results of total hip replacement due to acetabular fractures.
This study aims to evaluate short-term results of total hip replacement performed for post-traumatic osteoarthritis and/or femoral head necrosis caused by acetabular fractures. We performed 39 arthroplasties due to acetabular fractures on 25 male and 14 female patients during the course of a five-year period. The mean age of the patients was 45 years (range 25 to 73 years) at the time of surgery. Cemented cup was implanted in 29 patients and uncemented cup in 10 patients. Bone replacement was indicated in eight patients for different degrees of acetabular deformities. Implantation of an acetabular socket was indicated in six patients. The evaluation was based on the Harris hip score (HHS). The mean HHS score was 42 prior to arthroplasty and 81 after arthroplasty. Repeated surgery was required for infection in two patients. Dislocation of the prosthesis occurred in three patients, deep venous thrombosis in one patient and the lesion of the sciatic nerve in one patient after surgery. Our study results suggest that the selection of the cup type depends on the condition and bone deformity secondary to acetabular fracture. Surgical interventions are technically more difficult, and take longer with a high rate of the postoperative complications and prolonged rehabilitation period, compared to arthroplasties for degenerative hip diseases.


A flexible model for multivariate interval-censored survival times with complex correlation structure.
We focus on the analysis of multivariate survival times with highly structured interdependency and subject to interval censoring. Such data are common in developmental genetics and genetic epidemiology. We propose a flexible mixed probit model that deals naturally with complex but uninformative censoring. The recorded ages of onset are treated as possibly censored ordinal outcomes with the interval censoring mechanism seen as arising from a coarsened measurement of a continuous variable observed as falling between subject-specific thresholds. This bypasses the requirement for the failure times to be observed as falling into non-overlapping intervals. The assumption of a normal age-of-onset distribution of the standard probit model is relaxed by embedding within it a multivariate Box-Cox transformation whose parameters are jointly estimated with the other parameters of the model. Complex decompositions of the underlying multivariate normal covariance matrix of the transformed ages of onset become possible. The new methodology is here applied to a multivariate study of the ages of first use of tobacco and first consumption of alcohol without parental permission in twins. The proposed model allows estimation of the genetic and environmental effects that are shared by both of these risk behaviours as well as those that are specific.


Absence of Cushingoid phenotype in a patient with Cushing's disease due to defective cortisone to cortisol conversion.
Cushing's syndrome invariably presents with a classical phenotype comprising central adiposity, prominence of dorsal, supraclavicular and temporal fat pads, bruising, abdominal striae, proximal myopathy, and hypertension. We report the case of a 20-yr-old student with pituitary-dependent Cushing's syndrome who was spared this classical phenotype because of a defect in the peripheral conversion of cortisone to cortisol. She presented to her general practitioner with secondary amenorrhea. Clinical examination revealed normal fat distribution (body mass index, 20.9 kg/m(2)), absence of hirsutism, myopathy, or bruising; her blood pressure ranged from 115/70 to 122/82 mm Hg. She was investigated for biochemical hypercortisolemia because of a mildly elevated random circulating cortisol (serum cortisol, 661 nmol/liter). Cushing's syndrome was confirmed on the basis of repeatedly elevated urinary free cortisols (831-1049; reference range, <350 nmol/24 h), failure of low-dose dexamethasone suppression (611 nmol/liter) and loss of circadian cortisol secretion. Investigations suggested Cushing's disease; there was suppression after high-dose dexamethasone (<20 nmol/liter) and a 950% increase in ACTH after stimulation with CRH. Pituitary magnetic resonance imaging revealed a 3-mm adenoma within the pituitary gland. Urinary corticosteroid metabolites were analyzed by gas chromatography-mass spectrometry and demonstrated a decreased THF+allo-THF/THE ratio of 0.66 (mean +/- SE in Cushing's disease, 1.74 +/- 0.24) suggesting a defect in 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), an enzyme that converts the inactive glucocorticoid cortisone to active cortisol. Transphenoidal microadenomectomy was performed, and histology confirmed the diagnosis of a corticotroph adenoma. Postoperatively, serum cortisol was undetectable and replacement therapy was commenced. Subsequent investigations revealed a significantly impaired ability to convert an oral dose of cortisone acetate (25 mg) to cortisol, reduced serum cortisol to cortisone ratios, and a reduced serum half-life for cortisol (57.3 min). These results provide strong evidence for a partial defect in 11beta-HSD1 activity and concomitant increase in cortisol clearance rate. We have described a case of Cushing's disease that failed to present with a classical phenotype, and we postulate that this is due to a partial defect of 11beta-HSD1 activity, the defect in cortisone to cortisol conversion increasing cortisol clearance and thus protecting the patient from the effects of cortisol excess. This observation may help to explain individual susceptibility to the adverse effects of glucocorticoids.


Origins of concentration gradients for diffusiophoresis.
Fluid transport that is driven by gradients of pressure, gravity, or electro-magnetic potential is well-known and studied in many fields. A subtler type of transport, called diffusiophoresis, occurs in a gradient of chemical concentration, either electrolyte or non-electrolyte. Diffusiophoresis works by driving a slip velocity at the fluid-solid interface. Although the mechanism is well-known, the diffusiophoresis mechanism is often considered to be an esoteric laboratory phenomenon. However, in this article we show that concentration gradients can develop in a surprisingly wide variety of physical phenomena - imposed gradients, asymmetric reactions, dissolution, crystallization, evaporation, mixing, sedimentation, and others - so that diffusiophoresis is in fact a very common transport mechanism, in both natural and artificial systems. We anticipate that in georeservoir extractions, physiological systems, drying operations, laboratory and industrial separations, crystallization operations, membrane processes, and many other situations, diffusiophoresis is already occurring - often without being recognized - and that opportunities exist for designing this transport to great advantage.


Musical Meter Modulates the Allocation of Attention across Time.
Dynamic attending theory predicts that attention is allocated hierarchically across time during processing of hierarchical rhythmic structures such as musical meter. ERP research demonstrates that attention to a moment in time modulates early auditory processing as evidenced by the amplitude of the first negative peak (N1) approximately 100 msec after sound onset. ERPs elicited by tones presented at times of high and low metric strength in short melodies were compared to test the hypothesis that hierarchically structured rhythms direct attention in a manner that modulates early perceptual processing. A more negative N1 was observed for metrically strong beats compared with metrically weak beats; this result provides electrophysiological evidence that hierarchical rhythms direct attention to metrically strong times during engaged listening. The N1 effect was observed only on fast tempo trials, suggesting that listeners more consistently invoke selective processing based on hierarchical rhythms when sounds are presented rapidly. The N1 effect was not modulated by musical expertise, indicating that the allocation of attention to metrically strong times is not dependent on extensive training. Additionally, changes in P2 amplitude and a late negativity were associated with metric strength under some conditions, indicating that multiple cognitive processes are associated with metric perception.


How Disorder-Specific are Depressive Attributions? A Comparison of Individuals with Depression, Post-Traumatic Stress Disorder and Healthy Controls.
Depressed individuals tend to assign internal, stable, and global causes to negative events. The present study investigated the specificity of this effect to depression and compared depressive attributional styles of individuals with major depression (MD), post-traumatic stress disorder (PTSD), and healthy controls. We indexed attributional style using the depressive attributions questionnaire in 164 participants. Additionally, we assessed appraisals characteristic of PTSD using the post-traumatic cognitions inventory (PTCI), depressive rumination, trauma history, and depression and PTSD symptom severity. Individuals with MD endorsed a depressive attributional style to a greater extent than both individuals with PTSD, who were not depressed, and healthy controls. Depressive attributional style was associated with the severity of depressive and PTSD symptoms, number and distress of traumatic experiences, frequency of rumination, and post-traumatic cognitions. Depressive attributions and PTCI appraisals independently predicted MD and PTSD symptom severity. They may thus be useful in predicting MD and PTSD, and should be targeted in psychological treatments of these conditions.


Behavior of phenols and phenoxyacids on a bisphenol-A imprinted polymer. Application for selective solid-phase extraction from water and urine samples.
A molecularly imprinted polymer (MIP), obtained by precipitation polymerisation with 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as cross-linker, and bisphenol-A (BPA) as template, was prepared. The binding site configuration of the BPA-MIP was examined using Scatchard analysis. Moreover, the behaviour of the BPA-MIP for the extraction of several phenolic compounds (bisphenol-A, bisphenol-F, 4-nitrophenol, 3-methyl-4-nitrophenol) and phenoxyacid herbicides such as 2,4-D, 2,4,5-T and 2,4,5-TP has been studied in organic and aqueous media in the presence of other pesticides in common use. It was possible to carry out the selective preconcentration of the target analytes from the organic medium with recoveries of higher than 70%. In an aqueous medium, hydrophobic interactions were found to exert a remarkably non-specific contribution to the overall binding process. Several parameters affecting the extraction efficiency of the BPA-MIP were evaluated to achieve the selective preconcentration of phenols and phenoxyacids from aqueous samples. The possibility of using the BPA-MIP as a selective sorbent to preconcentrate these compounds from other samples such as urine and river water was also explored.


Recent Work on the Nature and Development of Delusions.
In this paper we review two debates in the current literature on clinical delusions. One debate is about what delusions are. If delusions are beliefs, why are they described as failing to play the causal roles that characterise beliefs, such as being responsive to evidence and guiding action? The other debate is about how delusions develop. What processes lead people to form delusions and maintain them in the face of challenges and counter-evidence? Do the formation and maintenance of delusions require abnormal experience alone, or also reasoning biases or deficits? We hope to show that the focus on delusions has made a substantial contribution to the philosophy of the mind and continues to raise issues that are central to defining the concept of belief and gaining a better understanding of how people process information and learn about the world.


Obstacles to prompt and effective malaria treatment lead to low community-coverage in two rural districts of Tanzania.
Malaria is still a leading child killer in sub-Saharan Africa. Yet, access to prompt and effective malaria treatment, a mainstay of any malaria control strategy, is sub-optimal in many settings. Little is known about obstacles to treatment and community-effectiveness of case-management strategies. This research quantified treatment seeking behaviour and access to treatment in a highly endemic rural Tanzanian community. The aim was to provide a better understanding of obstacles to treatment access in order to develop practical and cost-effective interventions. We conducted community-based treatment-seeking surveys including 226 recent fever episodes in 2004 and 2005. The local Demographic Surveillance System provided additional household information. A census of drug retailers and health facilities provided data on availability and location of treatment sources. After intensive health education, the biomedical concept of malaria has largely been adopted by the community. 87.5% (78.2-93.8) of the fever cases in children and 80.7% (68.1-90.0) in adults were treated with one of the recommended antimalarials (at the time SP, amodiaquine or quinine). However, only 22.5% (13.9-33.2) of the children and 10.5% (4.0-21.5) of the adults received prompt and appropriate antimalarial treatment. Health facility attendance increased the odds of receiving an antimalarial (OR = 7.7) but did not have an influence on correct dosage. The exemption system for under-fives in public health facilities was not functioning and drug expenditures for children were as high in health facilities as with private retailers. A clear preference for modern medicine was reflected in the frequent use of antimalarials. Yet, quality of case-management was far from satisfactory as was the functioning of the exemption mechanism for the main risk group. Private drug retailers played a central role by complementing existing formal health services in delivering antimalarial treatment. Health system factors like these need to be tackled urgently in order to translate the high efficacy of newly introduced artemisinin-based combination therapy (ACT) into equitable community-effectiveness and health-impact.


Response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to long-term administration of captopril in patients with severe, treatment-resistant malignant hypertension.
1. The response of arterial blood pressure, plasma renin activity and plasma aldosterone concentration to inhibition of angiotensin I converting enzyme (kininase II) with captopril has been studied in patients with severe, treatment-resistant, malignant hypertension. 2. Nine patients with a past history of severe hypertension, supine diastolic blood pressure greater than 120 mmHg before conventional antihypertensive therapy and resistant to conventional antihypertensive therapy were studied. 3. Captopril administration resulted in a marked decrease in arterial blood pressure and plasma aldosterone concentration and an increase in plasma renin activity. 4. Although arterial blood pressure remained significantly below the values observed during the control period, pressure did tend to increase again after 3 days. Addition of hydrochlorothiazide kept arterial pressure significantly below pretreatment control values.


Omega-3 Fatty Acid-Enriched Fish Oil and Selenium Combination Modulates Endoplasmic Reticulum Stress Response Elements and Reverses Acquired Gefitinib Resistance in HCC827 Lung Adenocarcinoma Cells.
Non-small cell lung cancer (NSCLC)-carrying specific epidermal growth factor receptor (EGFR) mutations can be effectively treated by a tyrosine kinase inhibitor such as gefitinib. However, the inevitable development of acquired resistance leads to the eventual failure of therapy. In this study, we show the combination effect of omega-3 fatty acid-enriched fish oil (FO) and selenium (Se) on reversing the acquired gefitinib-resistance of HCC827 NSCLC cells. The gefitinib-resistant subline HCC827GR possesses lowered proapoptotic CHOP (CCAAT/enhancer-binding protein homologous protein) and elevated cytoprotective GRP78 (glucose regulated protein of a 78 kDa molecular weight) endoplasmic reticulum (ER) stress response elements, and it has elevated β-catenin and cyclooxygenase-2 (COX-2) levels. Combining FO and Se counteracts the above features of HCC827GR cells, accompanied by the suppression of their raised epithelial-to-mesenchymal transition (EMT) and cancer stem markers, such as vimentin, AXL, N-cadherin, CD133, CD44, and ABCG2. Accordingly, an FO and Se combination augments the gefitinib-mediated growth inhibition and apoptosis of HCC827GR cells, along with the enhanced activation of caspase -3, -9, and ER stress-related caspase-4. Intriguingly, gefitinib further increases the elevated ABCG2 and cancer stem-like side population in HCC827GR cells, which can also be diminished by the FO and Se combination. The results suggest the potential of combining FO and Se in relieving the acquired resistance of NSCLC patients to targeted therapy.


DNA damage and biological expression of adenovirus: a comparison of liquid versus frozen conditions of exposure to gamma rays.
Human adenovirus type 2 (Ad 2) was irradiated with 137Cs gamma rays in the liquid state at 0 degree C. DNA breaks were correlated with the inactivation of several viral functions and compared to results obtained previously for irradiation of Ad 2 under frozen conditions at -75 degrees C. Irradiation at 0 degree C induced 170 +/- 20 single-strand breaks and 2.6 +/- 0.4 double-strand breaks/Gy/10(12) Da in the viral DNA. Viral adsorption to human KB cells was inactivated with a D0 of 9.72 +/- 1.18 kGy, whereas the inactivation of Ad 2 plaque formation had a D0 of 0.99 +/- 0.14 or 1.1 +/- 0.29 kGy when corrected for the effect of radiation on virus adsorption. For the adsorbed virus, an average of 4.3 +/- 1.7 single-strand and 0.065 +/- 0.02 double-strand breaks were induced in the viral DNA per lethal hit. In contrast, irradiation of Ad 2 at -75 degrees C results in 2.6- to 3.4-fold less DNA breakage per Gy and a 5.6-fold increase in D0 for plaque formation of the adsorbed virus. Furthermore, although host cell reactivation (HCR) of Ad 2 viral structural antigen production for irradiated virus was substantially reduced in the xeroderma pigmentosum fibroblast strain (XP25RO) compared to normal strains for irradiation at -75 degrees C (57% HCR), it was only slightly reduced compared to normal for irradiation at 0 degree C (88% HCR). These results indicate that the spectrum of DNA damage is both quantitatively and qualitatively different for the two conditions of irradiation.


Attending work or not when sick - what makes the decision? A qualitative study among car mechanics.
High prevalence of sickness absence in countries with generous welfare schemes has generated debates on mechanisms that may influence workers' decisions about calling in sick for work. Little is known about the themes at stake during the decision-making process for reaching the choice of absence or attendance when feeling ill. The aim of the study was to examine decisions of absence versus attendance among car mechanics when feeling ill. Interviews with 263 male car mechanics from 19 companies were used for the study, analysed by systematic text condensation and presented as descriptions and quotations of experiences and opinions. Three major themes were at stake during the decision-making process: 1) Experienced degree of illness, focusing on the present health condition and indicators of whether you are fit for work or not; 2) daily life habits, where attending work was a daily routine, often learned from childhood; 3) the importance of the job, with focus on the importance of work, colleagues, customers and work environment. The car mechanics expressed a strong will to attend work in spite of illness. Knowledge about attitudes and dilemmas in reaching the decision regarding sickness absence or sickness attendance is useful in the prevention of sickness absence.


Photooxidation Reactions of Ethyl 2-Methylpropionate (E2MP) and Ethyl 2,2-Dimethylpropionate (E22DMP) Initiated by OH Radicals: An Experimental and Computational Study.
The relative rate (RR) technique was used for the measurement of OH-initiated photooxidation reactions of ethyl 2-methylpropionate (E2MP) and ethyl 2,2-dimethylpropionate (E22DMP) in the temperature range of 268-363 K at 760 Torr. In addition to this, the thermodynamic and kinetic parameters for the title reactions were theoretically investigated using CCSD(T)/cc-pVTZ//M06-2X/6-311++G(2d,2p) level of theory in the temperature range of 200-400 K using canonical variational transition state theory (CVT) in combination with small curvature tunneling (SCT) method. The rate coefficients at (298 ± 2) K were measured to be kE2MP+OH = (2.71 ± 0.79) × 10-12 cm3 molecule-1 s-1 and kE22DMP+OH = (2.58 ± 0.80) × 10-12 cm3 molecule-1 s-1. The degradation mechanisms for the title reactions were investigated in the presence of O2 using gas chromatography with mass spectrometry (GC-MS) and gas chromatography with infrared spectroscopy (GC-IR). From the recognized products, the possible product degradation mechanisms were predicted. In addition to this, the atmospheric lifetimes (ALs), lifetime-corrected radiative forcing (RF), global warming potential (GWPs) and photochemical ozone creation potentials (POCPs) were calculated to further understand the environmental impact of these molecules on the Earth's troposphere.


From indication to decision: A hierarchical approach to model the chemotactic behavior of Escherichia coli.
Reducing the complex behavior of living entities to its underlying physical and chemical processes is a formidable task in biology. Complex behaviors can be characterized as decision making: the ability to process the incoming information via an intracellular network and act upon this information to choose appropriate strategies. Motility is one such behavior that has been the focus many modeling efforts in the past. Our aim is to reduce the chemotactic behavior in Escherichia coli to its molecular constituents in order to paint a comprehensive and end-to-end picture of this intricate behavior. We utilize a hierarchical approach, consisting of three layers, to achieve this goal: at the first level, chemical reactions involved in chemotaxis are simulated. In the second level, the chemical reactions give rise to the mechanical movement of six independent flagella. At the last layer, the two lower layers are combined to allow a digital bacterium to receive information from its environment and swim through it with verve. Our results are in concert with the experimental studies concerning the motility of E.coli cells. In addition, we show that our detailed model of chemotaxis is reducible to a non-homogeneous Markov process.


Loss of locus coeruleus neurons and reduced startle in parkin null mice.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized pathologically by degeneration of catecholaminergic neurons of the substantia nigra pars compacta and locus coeruleus, among other regions. Autosomal-recessive juvenile Parkinsonism (ARJP) is caused by mutations in the PARK2 gene coding for parkin and constitutes the most common familial form of PD. The majority of ARJP-associated parkin mutations are thought to be loss of function-mutations; however, the pathogenesis of ARJP remains poorly understood. Here, we report the generation of parkin null mice by targeted deletion of parkin exon 7. These mice show a loss of catecholaminergic neurons in the locus coeruleus and an accompanying loss of norepinephrine in discrete regions of the central nervous system. Moreover, there is a dramatic reduction of the norepinephrine-dependent startle response. The nigrostriatal dopaminergic system does not show any impairment. This mouse model will help gain a better understanding of parkin function and the mechanisms underlying parkin-associated PD.


The new research ethic: will oversight requirements sink forensic research?
The conduct of research with human participants is facing increased scrutiny from government, media, and academic sources. Research oversight is consequently increasing dramatically as education and accreditation movements gain momentum. Institutional review boards themselves are undergoing significant changes in organization and accountability, implementing new tools to monitor investigator compliance. This article describes the causes of recent calls for increased scrutiny, the resultant trends in research oversight, and the general lack of preparation for increased costs in the public sector. These are costs that will be felt acutely in the forensic setting as diminishing state budgets affect hospitals, universities, and correctional institutions.


The effects of grouping on speed discrimination thresholds in adults, typically developing children, and children with autism.
Adult observers show elevated speed discrimination thresholds when comparing the speeds of objects moving across a boundary compared to those moving parallel to a boundary (Verghese & McKee, 2006)-an effect that has been attributed to grouping processes in conjunction with a prior for smooth motion. Here, we extended Verghese and McKee's (2006) paradigm to typically developing children (n = 35) and children with autism (n = 26) and compared their performance with that of typical adults (n = 19). Speed discrimination thresholds were measured in three conditions: (a) with dots moving parallel to a boundary, (b) with dots moving perpendicular to a boundary, and (c) with dots in each stimulus half moving in orthogonal, oblique directions. As expected, participants had higher speed discrimination thresholds when dots appeared to cross a boundary compared to when dots moved parallel to the boundary. However, participants had even higher thresholds when dots moved in oblique, orthogonal directions, where grouping should be minimal. All groups of participants showed a similar pattern of performance across conditions although children had higher thresholds than adult participants overall. We consider various explanations for the pattern of performance obtained, including enhanced sensitivity for shearing motions and reduced sensitivity for discriminating different directions. Our results demonstrate that the speed discrimination judgments of typically developing children and children with autism are similarly affected by spatial configuration as those of typical adults and provide further evidence that speed discrimination is unimpaired in children with autism.


Buspirone: review of its pharmacology and current perspectives on its mechanism of action.
Buspirone is a novel anxiolytic agent unrelated to the benzodiazepines in structure or pharmacologic properties. Extensive clinical studies have shown buspirone to be effective in the treatment of anxiety, with efficacy comparable to diazepam or clorazepate. Buspirone exhibits a unique pharmacologic profile in that it alleviates anxiety without causing sedation or functional impairment and does not promote abuse or physical dependence. Furthermore, preclinical studies have shown that buspirone does not possess anticonvulsant or muscle relaxant properties and does not interact significantly with central nervous system depressants. Biochemical and electrophysiologic studies indicate that buspirone alters monoaminergic and GABAergic systems in a manner different from that of the benzodiazepines. The uniform depressant action of the benzodiazepines upon serotonergic, noradrenergic, and dopaminergic cell firing may result from their facilitatory effect on gamma-aminobutyric acid and its known inhibitory influence in these monoaminergic areas. Unlike the benzodiazepines, buspirone exerts a differential influence upon monoaminergic neuronal activity, suppressing serotonergic activity while enhancing dopaminergic and noradrenergic cell firing. The mechanism of action of buspirone challenges the notion that only one neurotransmitter mediates anxiety. The interaction with multiple neurotransmitters at multiple brain sites suggests that buspirone may alter diverse activities within a "neural matrix of anxiety." In contrast to the benzodiazepines, buspirone orchestrates activity within this neural matrix to achieve effective treatment of anxiety while preserving arousal and attentional processes.


Remodelling of spared proprioceptive circuit involving a small number of neurons supports functional recovery.
Studies show that limited functional recovery can be achieved by plasticity and adaptation of the remaining circuitry in partial injuries in the central nervous system, although the new circuits that arise in these contexts have not been clearly identified or characterized. We show here that synaptic contacts from dorsal root ganglions to a small number of dorsal column neurons, a caudal extension of nucleus gracilis, whose connections to the thalamus are spared in a precise cervical level 1 lesion, underwent remodeling over time. These connections support proprioceptive functional recovery in a conditioning lesion paradigm, as silencing or eliminating the remodelled circuit completely abolishes the recovered proprioceptive function of the hindlimb. Furthermore, we show that blocking repulsive Wnt signalling increases axon plasticity and synaptic connections that drive greater functional recovery.


Parviflorals A-F, trinorcadalenes and bis-trinorcadalenes from the roots of Decaschistia parviflora.
Trinorcadalenes, parviflorals A and B (1 and 2), and four bis-trinorcadalenes, parviflorals C-F (3-6), together with the known trinorcadalenes, syriacusins A (7) and C (8), scopoletin (9) and stigmasterol were isolated from roots of Decaschistia parviflora. Their structures were established by spectroscopic techniques. The CD spectra of the bis-trinorcadalenes (3-6) established their absolute configurations at the binaphthyl axis. Further, structure 6 was confirmed by a single-crystal X-ray crystallographic analysis. Compounds 2 and 6 showed antimalarial activity against Plasmodium falciparum with IC50 values of 11.45 and 6.85 μM, respectively. Compounds 1, 5, 7 and 8 also exhibited weak antifungal activity against Candida albicans, with IC50 values in the range of 37.03-197.68 μM. Compounds 1-3 and 5-8 showed weak antimycobacterial activity against Mycobacterium tuberculosis with MIC values in the range of 54.30-192.13 μM. In addition, several of these compounds possessed cytotoxicity towards the cancer cell lines, KB, MCF7 and NCI-H187 with IC50 values in the range of 2.20-90.09 μM.


Effect of Temperature on Sporulation of Botryosphaeria dothidea, B. obtusa, and B. rhodina.
Three Botryosphaeria spp. were grown on autoclaved apple and peach stems in cotton-plugged tubes with constant moisture at 6, 12, 18, 24, and 30°C to determine the effect of temperature on sporulation. Number of conidia per pycnidium was determined weekly from 4 to 10 weeks after inoculation. The experiment was repeated three times. Maximum sporulation occurred at 24°C with B. dothidea and at 18 and 24°C with B. obtusa. Spore production of both fungi showed a quadratic curvilinear response to temperature. Pycnidia were erumpent, typical of their habit in nature. Maximum sporulation of B. rhodina occurred at 12, 24, and 30°C instead of at a distinctive peak. Of the three fungi, B. rhodina produced the greatest number of conidia per pycnidium at all temperatures. Mycelia and pycnidia of B. rhodina grew on top of the bark, which is atypical of their habit in nature. For spore production by B. dothidea, there was a significant interaction between temperature and time. Maximum sporulation over the 10-week period occurred in week 4 and/or 6 for B. dothidea at 12, 18, and 24°C, with a linear response at 12 and 24°C (P ≤0.05). Conidial maturation of B. obtusa and B. rhodina had a quadratic curvilinear response due to temperature, with a maximum maturation at 12, 18, and 24°C with B. obtusa and at 24°C with B. rhodina. Spore maturation would affect longevity of conidial viability. Maximum spore production over time and percent pigmented spores over time by B. obtusa, and spore maturation over time by B. rhodina occurred in weeks 8, 9, and 10 with a significant linear response (P ≤ 0.05). All three Botryosphaeria spp. produced conidia over the 6 to 30°C range and over the 7-week period (weeks 4 to 10), with maximum sporulation or spore maturation at 18 to 24°C.


Bone graft options for spinal fusion following resection of spinal column tumors: systematic review and meta-analysis.
OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I2 values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I2 = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.


Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association.
Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.


Quantifying sociodemographic heterogeneities in the distribution of Aedes aegypti among California households.
The spread of Aedes aegypti in California and other regions of the U.S. has increased the need to understand the potential for local chains of Ae. aegypti-borne virus transmission, particularly in arid regions where the ecology of these mosquitoes is less understood. For public health and vector control programs, it is helpful to know whether variation in risk of local transmission can be attributed to socio-demographic factors that could help to target surveillance and control programs. Socio-demographic factors have been shown to influence transmission risk of dengue virus outside the U.S. by modifying biting rates and vector abundance. In regions of the U.S. where Ae. aegypti have recently invaded and where residential areas are structured differently than those in the tropics where Ae. aegypti are endemic, it is unclear how socio-demographic factors modify the abundance of Ae. aegypti populations. Understanding heterogeneities among households in Ae. aegypti abundance will provide a better understanding of local vectorial capacity and is an important component of understanding risk of local Ae. aegypti-borne virus transmission. We conducted a cross-sectional study in Los Angeles County, California during summer 2017 to understand the causes of variation in relative abundance of Ae. aegypti among households. We surveyed 161 houses, representing a wide range of incomes. Surveys consisted of systematic adult mosquito collections, inspections of households and properties, and administration of a questionnaire in English or Spanish. Adult Ae. aegypti were detected at 72% of households overall and were found indoors at 12% of households. An average of 3.1 Ae. aegypti were collected per household. Ae. aegypti abundance outdoors was higher in lower-income neighborhoods and around older households with larger outdoor areas, greater densities of containers with standing water, less frequent yard maintenance, and greater air-conditioner use. We also found that Ae. aegypti abundance indoors was higher in households that had less window and door screening, less air-conditioner usage, more potted plants indoors, more rain-exposed containers around the home, and lower neighborhood human population densities. Our results indicate that, in the areas of southern California studied, there are behavioral and socio-demographic determinants of Ae. aegypti abundance, and that low-income households could be at higher risk for exposure to Ae. aegypti biting and potentially greater risk for Zika, dengue, and chikungunya virus transmission if a local outbreak were to occur.


Contribution of Leg-Muscle Forces to Paddle Force and Kayak Speed During Maximal-Effort Flat-Water Paddling.
The purpose was to investigate the contribution of leg-muscle-generated forces to paddle force and kayak speed during maximal-effort flat-water paddling. Five elite male kayakers at national and international level participated. The participants warmed up at progressively increasing speeds and then performed a maximal-effort, nonrestricted paddling sequence. This was followed after 5 min rest by a maximal-effort paddling sequence with the leg action restricted--the knee joints "locked." Left- and right-side foot-bar and paddle forces were recorded with specially designed force devices. In addition, knee angular displacement of the right and left knees was recorded with electrogoniometric technique, and the kayak speed was calculated from GPS signals sampled at 5 Hz. The results showed that reduction in both push and pull foot-bar forces resulted in a reduction of 21% and 16% in mean paddle-stroke force and mean kayak speed, respectively. Thus, the contribution of foot-bar force from lower-limb action significantly contributes to kayakers' paddling performance.


Weak interspecific interactions in a sagebrush steppe? Conflicting evidence from observations and experiments.
Stable coexistence requires intraspecific limitations to be stronger than interspecific limitations. The greater the difference between intra- and interspecific limitations, the more stable the coexistence, and the weaker the competitive release any species should experience following removal of competitors. We conducted a removal experiment to test whether a previously estimated model, showing surprisingly weak interspecific competition for four dominant species in a sagebrush steppe, accurately predicts competitive release. Our treatments were (1) removal of all perennial grasses and (2) removal of the dominant shrub, Artemisia tripartita. We regressed survival, growth, and recruitment on the locations, sizes, and species identities of neighboring plants, along with an indicator variable for removal treatment. If our "baseline" regression model, which accounts for local plant-plant interactions, accurately explains the observed responses to removals, then the removal coefficient should be non-significant. For survival, the removal coefficients were never significantly different from zero, and only A. tripartita showed a (negative) response to removals at the recruitment stage. For growth, the removal treatment effect was significant and positive for two species, Poa secunda and Pseudoroegneria spicata, indicating that the baseline model underestimated interspecific competition. For all three grass species, population models based on the vital rate regressions that included removal effects projected 1.4- to 3-fold increases in equilibrium population size relative to the baseline model (no removal effects). However, we found no evidence of higher response to removal in quadrats with higher pretreatment cover of A. tripartita, or by plants experiencing higher pre-treatment crowding by A. tripartita, raising questions about the mechanisms driving the positive response to removal. While our results show the value of combining observations with a simple removal experiment, more tightly controlled experiments focused on underlying mechanisms may be required to conclusively validate or reject predictions from phenomenological models.


Geographical location influences the composition of the gut microbiota in wild house mice (Mus musculus domesticus) at a fine spatial scale.
The composition of the mammalian gut microbiota can be influenced by a multitude of environmental variables such as diet and infections. Studies investigating the effect of these variables on gut microbiota composition often sample across multiple separate populations and habitat types. In this study we explore how variation in the gut microbiota of the house mouse (Mus musculus domesticus) on the Isle of May, a small island off the east coast of Scotland, is associated with environmental and biological factors. Our study focuses on the effects of environmental variables, specifically trapping location and surrounding vegetation, as well as the host variables sex, age, body weight and endoparasite infection, on the gut microbiota composition across a fine spatial scale in a freely interbreeding population. We found that differences in gut microbiota composition were significantly associated with the trapping location of the host, even across this small spatial scale. Sex of the host showed a weak association with microbiota composition. Whilst sex and location could be identified as playing an important role in the compositional variation of the gut microbiota, 75% of the variation remains unexplained. Whereas other rodent studies have found associations between gut microbiota composition and age of the host or parasite infections, the present study could not clearly establish these associations. We conclude that fine spatial scales are important when considering gut microbiota composition and investigating differences among individuals.


Growth hormone receptor messenger ribonucleic acid distribution in the adult male rat brain and its colocalization in hypothalamic somatostatin neurons.
The activity of both somatostatin (SS) and GH-releasing hormone (GHRH) neurons within several hypothalamic nuclei is regulated, in part, by the feedback effects of GH. However, whether GH, or its intermediate, insulin-like growth factor I, acts on these neurons to alter the synthesis and release of SS and GHRH is unknown. We argued that if GH itself acts directly on the brain to govern its own secretion, then regions of the brain containing SS and GHRH neurons may express the GH receptor gene. We tested this hypothesis by performing in situ hybridization for GH receptor messenger RNA (mRNA) and mapping its distribution in the brain. We observed GH receptor mRNA-containing cells in various brain regions including the thalamus, septal region, hippocampus, dentate gyrus, amygdala, and hypothalamus. Next we sought evidence for expression of the GH receptor mRNA by SS neurons in the hypothalamus. We addressed this by performing a double-label in situ hybridization to identify neurons expressing both SS mRNA and GH receptor mRNA. We report that SS neurons in the periventricular nucleus and in the paraventricular nucleus coexpress the GH receptor gene, whereas few, if any, of the SS neurons in the cortex express detectable amounts of the GH receptor mRNA. These findings suggest that GH acts directly on the brain and participates in the regulation of its own secretion through a direct action on hypothalamic SS neurons.


A high-fat diet influences insulin-stimulated posttransport muscle glucose metabolism in rats.
Because of a failure to detect significant quantities of intracellular glucose, it has been generally accepted that transport rather than phosphorylation is the rate-limiting process of muscle glucose metabolism under most (but not all) physiological conditions. Here, we have measured tissue free levels of the glucose analog 2-deoxy-D-glucose (2DG) in red quadriceps muscle of rats fed a high-fat diet (59% of energy from fat) for 3 weeks, to identify the barrier to insulin-stimulated glucose uptake previously seen in such animals. Measurements were performed on pentobarbital-anesthetized rats following exogenous infusion of radiolabeled 2DG. A glucose clamp was used to maintain plasma insulin at high physiological levels (approximately 120 mU/L). Three other treatment groups representing normal insulin action (chow-fed), extreme glucose uptake (maximal insulin stimulation + hyperglycemia), and insulin resistance with elevated free intracellular glucose (epinephrine infusion) were also studied for comparison. In chow-fed animals, no muscle free 2DG was detected, confirming transport as the rate-limiting process. In fat-fed animals, a significant elevation in muscle free 2DG was observed (P < .01 v chow-fed controls). The elevation was similar in magnitude to that in epinephrine-infused rats, and implied a limitation of insulin action at a posttransport step. This result was confirmed with a more complex modeling analysis. We conclude that posttransport steps influence insulin-stimulated in vivo muscle glucose metabolism in long-term high-fat-fed rats.


The development and impact of insomnia on cancer survivors: a qualitative analysis.
To conduct the first qualitative analysis of the development and impact of insomnia on a cohort of cancer survivors. Twenty-one cancer survivors with a history of chronic insomnia contributed to four focus groups held at the University of Glasgow Sleep Research Centre. Participants' perceptions of the onset, evolution and effects of insomnia were elicited and qualitatively explored using content analysis. Most participants reported insomnia onset following cancer diagnosis. Participants who had a pre-existing insomnia reported that cancer diagnosis significantly aggravated their sleep complaint. Active cancer treatment was a major contributor to poor sleep quality due to the disruption of normal daily routines. This poor sleep pattern became persistent once active treatment had ceased and participants reported becoming particularly concerned about their sleep when they were discharged into follow-up cancer care. The impact of insomnia was significant for all participants in the study and six major areas emerged as being particularly affected; mood, physical health, relationships, sleep quality, sleep-related behaviour and cognition. The majority of cancer survivors in this study developed disturbed sleep as a result of cancer diagnosis and their sleep disruption was exacerbated by active cancer treatment. Insomnia also had a significant impact upon quality of life and these effects persisted long beyond the cessation of active anti-cancer therapy. Early identification of insomnia symptoms in cancer care settings must be a priority to ensure that sleep disturbance is not overlooked or poorly managed.


Mother-child bed-sharing in toddlerhood and cognitive and behavioral outcomes.
We examined the predictors and consequences of mother-child bed-sharing at 1, 2, and 3 years of age in a racially/ethnically and geographically diverse sample of low-income families across the United States. We analyzed data from 944 low-income families who had children assessed at 1, 2, 3, and 5 years of age. Mothers who were Hispanic and black were more likely to bed-share with children at ages 1, 2, and 3 years than other mothers. Maternal negative regard also predicted bed-sharing. Bed-sharing at ages 1 to 3 years was bivariately associated with poorer behavior and cognition at age 5 years. However, these associations lost significance when child and mother characteristics were controlled. There seem to be no negative associations between bed-sharing in toddlerhood and children's behavior and cognition at age 5 years.


Local recurrence detection following transanal excision facilitated by EUS-FNA.
Local excision is an alternative management approach for early rectal cancers and patients unfit for radical surgery. It is associated with a high local recurrence rate. Our aims were to evaluate the rate, pattern, method of local recurrence detection, the opportunity for salvage resection and finally to explore the utility of endoscopic ultrasound fine needle aspiration during surveillance. A retrospective, non-controlled, cohort study from a single tertiary referral center comprised of patients undergoing surveillance following a transanal excision. Post-operative surveillance was performed in 155 transanal excision patients of which 46 (30%) underwent =1 endoscopic ultrasound examinations. Intra and extra luminal recurrence (n=16/24; (67%)) was detected more frequently in the endoscopic ultrasound surveillance population, p=0.0008. Mucosal scar biopsy (n=10/16;63%) and endoscopic ultrasound fine needle aspiration (6/16; 38%) of either a lymph node or the deep rectal wall were the methods for establishing local recurrence. An unremarkable proctoscopy with endoscopic ultrasound fine needle aspiration positive cytological findings was noted in 4 (9%) of the patients. Local recurrence following transanal excision is often in an intraluminal location. Endoscopic ultrasound fine needle aspiration confirmed nodal metastases in mesenteric and extra mesenteric locations more frequently than subepithelial locations.


Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease.
Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty-five HD subjects and twenty-five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise.


Perioperative pain management for total knee arthroplasty.
Pain management following total knee arthroplasty (TKA) can be challenging. Inadequate pain management following TKA may inhibit rehabilitation, increase morbidity and mortality, decrease patient satisfaction, and lead to chronic persistent postsurgical pain. Traditionally the mainstay of postoperative pain management was opioids; however, the current recommendations to pain management emphasize a multimodal approach and minimizing opioids whenever possible. With careful planning and a multimodal analgesic approach instituted perioperatively, appropriate pain management following TKA can be achieved. Utilizing an extensive review of the literature, this article discusses the analgesic techniques available for the perioperative management of TKA.


The Influence of Time and Plant Species on the Composition of the Decomposing Bacterial Community in a Stream Ecosystem.
Foliar chemistry influences leaf decomposition, but little is known about how litter chemistry affects the assemblage of bacterial communities during decomposition. Here we examined relationships between initial litter chemistry and the composition of the bacterial community in a stream ecosystem. We incubated replicated genotypes of Populus fremontii and P. angustifolia leaf litter that differ in percent tannin and lignin, then followed changes in bacterial community composition during 28 days of decomposition using 16S rRNA gene-based pyrosequencing. Using a nested experimental design, the majority of variation in bacterial community composition was explained by time (i.e., harvest day) (R(2) = 0.50). Plant species, nested within harvest date, explained a significant but smaller proportion of the variation (R(2) = 0.03). Significant differences in community composition between leaf species were apparent at day 14, but no significant differences existed among genotypes. Foliar chemistry correlated significantly with community composition at day 14 (r = 0.46) indicating that leaf litter with more similar phytochemistry harbor bacterial communities that are alike. Bacteroidetes and β-proteobacteria dominated the bacterial assemblage on decomposing leaves, and Verrucomicrobia and α- and δ-proteobacteria became more abundant over time. After 14 days, bacterial diversity diverged significantly between leaf litter types with fast-decomposing P. fremontii hosting greater richness than slowly decomposing P. angustifolia; however, differences were no longer present after 28 days in the stream. Leaf litter tannin, lignin, and lignin: N ratios all correlated negatively with diversity. This work shows that the bacterial community on decomposing leaves in streams changes rapidly over time, influenced by leaf species via differences in genotype-level foliar chemistry.


Deaths among railroad trespassers. The role of alcohol in fatal injuries.
To describe the characteristics of persons killed by trains while trespassing (ie, using railroad property for activities unrelated to railroad operations). Case series obtained from records of the state medical examiner. North Carolina, 1990 through 1994. One hundred twenty-eight persons ranging in age from 7 to 84 years who were killed in 125 separate incidents. Of 224 railroad-related deaths during the study period, 128 cases (57%) involved trespassers. Trespasser fatalities typically involved unmarried male pedestrians 20 to 49 years of age with less than a high school education. Eighty-two percent of incidents occurred in the trespassers' county of residence, indicating that few deaths involved transients. Fatalities among railroad trespassers exhibited both geographic and temporal clustering. Seventy-eight percent of trespassers were killed while intoxicated (median alcohol level, 56 mmol/L [260 mg/dL]). Deaths among trespassers are the leading cause of railroad-related mortality in North Carolina. Greater efforts are needed to reduce this type of preventable injury. Prevention of trespasser fatalities is dependent on control of alcohol abuse, enforcement of existing laws, and education of the public regarding the dangers of railroad trespassing.


Application and Validation of a Determination Method Using Post-column Reaction Gas Chromatography of Nitrogen-containing Organic Compounds.
In this work, we applied post-column reaction gas chromatography (GC) using a flame ionization detector (FID) system to study nitrogen-containing organic compounds (NOCs). The results were subsequently validated. After separation by column, the target components were converted to carbon dioxide using an oxidizing catalyst and then reduced to methane, followed by detection using an FID. SI-traceable testing mixtures containing NOCs (isoprocarb, napropamide, and pendimethalin) were prepared by the gravimetric blending method. These mixtures were analyzed using a post-column reaction GC-FID system; standard materials of hydrocarbons were used as calibrants in this analysis. The determined values were compared with the values obtained for samples prepared at the corresponding concentrations, and statistical analyses were performed in all cases. It was shown that the determined and prepared values agreed well with each other within the uncertainty limits.


Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis.
Dabigatran etexilate has been investigated in three phase III trials for the prevention of venous thromboembolism (VTE). Health technology assessment agencies increasingly require meta-analyses of all relevant evidence for an intervention, if appropriate. The objective of this study was to perform a meta-analysis of efficacy and safety data for the recommended dose of dabigatran etexilate, 220 mg once daily (od), for VTE prophylaxis after total knee arthroplasty (TKA) and total hip arthroplasty (THA), and discuss the appropriateness of combining the data. Risk ratios (RR) for VTE and bleed end-points were estimated using fixed and random effects meta-analysis. Analyses were performed combining RE-MODEL and RE-NOVATE, which compared dabigatran etexilate with enoxaparin 40 mg od after TKA and THA, respectively, and also including RE-MOBILIZE, which compared dabigatran etexilate with enoxaparin 30 mg twice daily after TKA. Tests for statistical heterogeneity were performed using the Chi-squared statistic. No significant differences were detected between dabigatran etexilate and enoxaparin in any of the end-points analysed, either in the two trial analysis (all p > 0.15), or when all three trials were combined ( all p > 0.30). RRs (random effects) for the composite end-point total VTE and all-cause mortality were 0.95 [95% confidence intervals 0.82 - 1.10] and 1.05 [0.87 - 1.26] in the two and three trial analyses, respectively. Meta-analysis of RE-MODEL and RE-NOVATE supported the conclusions of the individual trials that dabigatran etexilate is non-inferior to enoxaparin 40 mg od, with a similar safety profile. Meta-analysis of all three trials found no significant differences between treatments in any of the end-points analysed. Heterogeneity between the trials cannot be ruled out.


Heterogeneity of normal human diploid fibroblasts: isolation and characterization of one phenotype.
Cultures of human diploid fibroblasts contain cells that respond to exposure to the first component of complement (C1) by initiating DNA synthesis and growth. The plasma membranes of these cells have specific binding sites for the C1q subcomponent of C1. A fluorescence-activated cell sorter was used to isolate a subset of cells with a high affinity for C1q, and the growth and synthesis activities of these high-affinity cells were studied after numerous replications in vitro. These cells synthesize DNA and grow faster than the parent cultures and low-affinity cells, and they produce two to three times as much protein. About 40 percent of their total protein synthesis activity is directed to collagen production, unusually high proportions of collagen types III and V being produced. These properties and the high affinity of the cells for C1q are retained for at least six cell transfers. This phenotype has the properties expected of fibroblasts in healing wounds and inflamed tissues.


Mitochondrial DNA copy number is regulated by DNA methylation and demethylation of POLGA in stem and cancer cells and their differentiated progeny.
Mitochondrial DNA (mtDNA) copy number is strictly regulated during differentiation so that cells with a high requirement for ATP generated through oxidative phosphorylation have high mtDNA copy number, whereas those with a low requirement have few copies. Using immunoprecipitation of DNA methylation on 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC), which distinguish between de novo DNA methylation and demethylation, respectively, we set out to determine whether DNA methylation at exon 2 of the human mtDNA-specific polymerase (DNA polymerase gamma A (POLGA)) regulates cell-specific mtDNA copy number in highly proliferative and terminally differentiated cells. Highly proliferative cancer and pluripotent and multipotent cells possessed low mtDNA copy number and were highly methylated at exon 2 of POLGA in contrast to post-mitotic cells. Unlike neural stem cells, cancer cells were unable to differentiate and remained extensively DNA methylated at exon 2 of POLGA. However, mtDNA depletion of cancer cells reduced DNA methylation at exon 2 of POLGA as they replenished mtDNA to form tumours in mice. Glioblastoma cells treated with the DNA demethylation agent 5-azacytidine over 28 days of astrocyte-induced differentiation demethylated exon 2 of POLGA leading to increased mtDNA copy number and expression of the astrocyte endpoint marker glial fibrillary acidic protein (GFAP). However, the demethylation agent vitamin C (VitC) was unable to sustain increased mtDNA copy number and differentiation, as was the case when VitC was withdrawn after short-term treatment. These data demonstrate that DNA demethylation of POLGA is an essential regulator of mtDNA copy number and cellular fate and that cancer cells are only able to modulate DNA methylation of POLGA and mtDNA copy number in the presence of a DNA demethylation agent that inhibits de novo methyltransferase 1 activity.


What is the best femoral fixation of hamstring autografts in anterior cruciate ligament reconstruction?: a meta-analysis.
Several methods are available for fixing the femoral side of a hamstring autograft in ACL reconstruction and the best method is unclear. Biomechanical studies have shown varying results with regard to fixation failure. We asked whether there were any differences with regard to graft failures and functional outcome measures with differing methods of femoral fixation of hamstring autografts in ACL reconstruction. We systematically reviewed the literature using PubMed, MEDLINE, Scopus, and Cochrane Controlled Trial Register databases with regard to interference screw fixation (aperture fixation) versus noninterference screw fixation (fixation away from the joint line). A meta-analysis was performed of those studies reporting on surgical failures and postoperative International Knee Documentation Committee score. Eight studies met our inclusion criteria of Level I or II evidence. Use of interference screws for femoral fixation resulted in a trend toward decreased risk of surgical failure (relative risk = 0.57; confidence interval, 0.1678-1.0918). When only Level I trials were evaluated, the same trend was noted toward a decreased risk of surgical failures using femoral interference screws (relative risk = 0.52; confidence interval, 0.1794-1.3122). There was no difference in postoperative International Knee Documentation Committee score with Level I and II studies (relative risk = 0.9940; confidence interval, 0.6230-1.5860) or only Level I studies (relative risk = 1.0380; confidence interval, 0.6381-1.6886). The literature suggests a trend toward decreased surgical failures with femoral fixation at the joint line with an interference screw. However, there is no difference when postoperative functional outcomes are compared. Future studies are needed with standardized fixation methods and outcomes assessment to determine the importance of femoral fixation.


Pitch processing sites in the human auditory brain.
Lateral Heschl's gyrus (HG), a subdivision of the human auditory cortex, is commonly believed to represent a general "pitch center," responding selectively to the pitch of sounds, irrespective of their spectral characteristics. However, most neuroimaging investigations have used only one specialized pitch-evoking stimulus: iterated-ripple noise (IRN). The present study used a novel experimental design in which a range of different pitch-evoking stimuli were presented to the same listeners. Pitch sites were identified by searching for voxels that responded well to the range of pitch-evoking stimuli. The first result suggested that parts of the planum temporale are more relevant for pitch processing than lateral HG. In some listeners, pitch responses occurred elsewhere, such as the temporo-parieto-occipital junction or prefrontal cortex. The second result demonstrated a different pattern of response to the IRN and raises the possibility that features of IRN unrelated to pitch might contribute to the earlier results. In conclusion, it seems premature to assign special status to lateral HG solely on the basis of neuroactivation patterns. Further work should consider the functional roles of these multiple pitch processing sites within the proposed network.


Pilot Test of a Theory-Based Instrument to Measure Nursing Informatics Leadership Skills.
Understanding organizational cultures helps leaders focus on the content, context and levels of perspective needed to be successful leaders in the area of nursing informatics. The Minnesota Nursing Informatics Leadership Inventory (MNILI) was developed to expand assessment options and tools in the area of nursing informatics leadership. This article describes the result of the pilot test of the instrument. Using an ordinal Likert scale (0 = not like me to 4 = very much like me), respondents rated 12 leadership skills associated with four types of cultures across four scenarios. Respondents preferred collaborative culture leadership skills across all scenarios and differentially preferred culture-specific skills by scenario. Overall, older and more experienced respondents were more satisfied as leaders (p = 0.003) and more often used a democratic leadership approach (empower and care about all voices; p = 0.012). In three of the four cultures, nursing informatics leaders reported preferred and collaborative leadership skills that matched the scenario. This study provides preliminary evidence for using the MNILI to assess the requisite variety of nursing informatics leadership skills. Further research is needed to understand the dynamic interactions between organizational culture and nursing informatics leadership that are informed by conscious leadership and attention to the requisite variety of leadership skills.


Regional cerebral blood flow changes in drug-resistant depressed patients following treatment with transcranial magnetic stimulation: a statistical parametric mapping analysis.
Changes of regional cerebral blood flow (rCBF) in five drug-resistant depressed patients were examined by single photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) before and after treatment with transcranial magnetic stimulation (TMS). The SPECT images were analysed with the Statistical Parametric Mapping (SPM) package. TMS administered in the region of the left dorsolateral prefrontal cortex (DLPFC) of the depressed patients was associated with an increase of rCBF at a focal region some distance from the stimulation site. No change was observed at any other remote region.


Nephritis-associated plasmin receptor and acute poststreptococcal glomerulonephritis: characterization of the antigen and associated immune response.
The role of nephritis-associated antigen as a virulence factor for acute poststreptococcal glomerulonephritis (APSGN) remains to be fully clarified. Nephritis-associated plasmin receptor (NAPlr) was previously isolated from group A streptococcus (GAS) and shown to bind plasmin(ogen). The nucleotide sequence of the naplr gene from GAS isolates obtained from patients with APSGN was determined. The sequence of the putative open reading frame (1011 bp) showed 99.8% identity among isolated strains. Homology screen revealed an exact match with streptococcal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). NAPlr exhibited GAPDH activity in zymography, and it activated the complement pathway in vitro. In APSGN kidney biopsy specimens, NAPlr was observed mainly in the early stage of the disease (1 to 14 d after onset) but was not colocalized with either C3 or IgG as assessed by double immunofluorescence staining. Sera of patients with APSGN, patients with GAS infection without renal involvement, nonrenal pediatric patients, and healthy adults as controls were assayed for anti-NAPlr antibody titers. Anti-NAPlr antibodies were present most frequently in APSGN sera, and antibody titers were also significantly higher than in patients with GAS infection alone or in other control patients. Moreover, antibody titers remained elevated during the entire 10-yr follow-up period.


OKT3 induction and steroid-free maintenance immunosuppression for treatment of high-risk heart transplant recipients.
A group of high-risk heart transplant patients (n = 35) were treated from May 1987 through June 1990, with murine-derived monoclonal CD3 antibody (OKT3) induction therapy and steroid-free maintenance immunosuppression. This group was compared with a group of transplant patients (n = 47) who were not considered high risk and who were treated simultaneously with triple-drug immunosuppression (cyclosporine, azathioprine, and prednisone). The 1- and 3-year actuarial survival rates were similar: 97% and 91% for the OKT3 and 92% and 85% for the triple-drug immunosuppression groups, respectively. The overall incidence of rejection was equal for both groups (56%). No rejection occurred during the OKT3 course and rejection episodes occurred significantly later in patients treated with OKT3, with a mean first rejection episode of 111 +/- 104 days versus 27 +/- 21 days for the triple-drug immunosuppression group (p less than or equal to 0.05). Bacterial infections were seen more frequently (29% vs 6% of the patients treated) in the early period (less than 3 months) in the OKT3 group (p = 0.01) and were associated with the use of mechanical assistance in this group. The incidence of late infections or cytomegalovirus disease was similar for both groups. Patients treated with OKT3 and subsequent steroid-free maintenance immunosuppression had no significant posttransplantation increases of serum cholesterol levels, and hypertension was less common. Initial hospitalization was longer (p less than or equal to 0.05) in the OKT3 group (23 +/- 19 vs 13 +/- 5 days) but after the initial discharge the number of hospital days for the first year was similar for both groups (8 +/- 14 vs 9 +/- 13 days). Ventricular function at 1 year after transplantation was similar for both groups with average ejection fraction of 57% and 59% for the OKT3 and triple-drug immunosuppression groups, respectively. In conclusion, high-risk patients treated with OKT3 and steroid-free maintenance immunosuppression were managed on smaller doses of immunosuppressive drugs in the early postoperative period, and had excellent long-term survival rates. In this group of patients, rejection was delayed and the incidence of hypercholesterolemia, hypertension, and steroid-induced complications was decreased. Such a regimen offers a relatively drug-free period in the early posttransplant stages and freedom from the long-term complications of steroids.


Co-exposure of ZnO nanoparticles and UV radiation to Daphnia magna and Danio rerio: Combined effects rather than protection.
The application of nanoparticles (NPs) in consumer products has been increasing over the past few years. Their release into the environment is likely to happen at any stage of production or during the use of products containing NPs. Zinc oxide NPs (ZnO-NP) are among the most-used NPs on the market due to its intrinsic properties, such as ultraviolet (UV) absorption. The aim of the present study was to assess the combined effects of ZnO-NP and UV radiation on 2 freshwater species: Daphnia magna and Danio rerio. The initial hypothesis was that the presence of ZnO-NP in the aquatic media would decrease the damaging effects of UV radiation for both species. The endpoints assessed for D. magna were immobilization, feeding inhibition, and reproduction output. For D. rerio, egg development was studied during 96 h and mortality, hatching delay, and abnormal development were the endpoints recorded. Combined exposures were designed based on the single toxicity of both stressors and analyzed based on the independent action concept and exploring possible deviations for synergism/antagonism, dose level, and dose ratio. Combined exposures with D. magna induced synergism on reproduction, decreasing the number of neonates produced more than expected based on both stressors' individual toxicity. Single exposures of D. rerio embryos to both stressors induced negative effects. The combined exposures caused a dose-ratio deviation pattern on mortality and hatching, with a synergism observed when ZnO-NP was the dominant stressor, changing to antagonism when UV radiation dominated the combined exposure. Regarding the results attained, studying ZnO toxicity under laboratory conditions may underestimate the risks when considering the potential interaction on effects when combined with UV radiation.


Psychometric properties of carer-reported outcome measures in palliative care: A systematic review.
Informal carers face many challenges in caring for patients with palliative care needs. Selecting suitable valid and reliable outcome measures to determine the impact of caring and carers' outcomes is a common problem. To identify outcome measures used for informal carers looking after patients with palliative care needs, and to evaluate the measures' psychometric properties. A systematic review was conducted. The studies identified were evaluated by independent reviewers (C.T.J.M., M.B., M.P.). Data regarding study characteristics and psychometric properties of the measures were extracted and evaluated. Good psychometric properties indicate a high-quality measure. The search was conducted, unrestricted to publication year, in the following electronic databases: Applied Social Sciences Index and Abstracts, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, EMBASE, PubMed, PsycINFO, Social Sciences Citation Index and Sociological Abstracts. Our systematic search revealed 4505 potential relevant studies, of which 112 studies met the inclusion criteria using 38 carer measures for informal carers of patients with palliative care needs. Psychometric properties were reported in only 46% (n = 52) of the studies, in relation to 24 measures. Where psychometric data were reported, the focus was mainly on internal consistency (n = 45, 87%), construct validity (n = 27, 52%) and/or reliability (n = 14, 27%). Of these, 24 measures, only four (17%) had been formally validated in informal carers in palliative care. A broad range of outcome measures have been used for informal carers of patients with palliative care needs. Little formal psychometric testing has been undertaken. Furthermore, development and refinement of measures in this field is required.